title: Binding of lactoferrin to IGBP1 triggers apoptosis in a lung adenocarcinoma cell line.
abstract: BACKGROUND
  Lactoferrin (Lf), an iron-binding protein present in mammalian secretions, plays important roles in cancer prevention by inducing apoptosis.
  
  
  METHODS
  PC-14 lung adenocarcinoma cells were exposed to bovine Lf (bLf) protein and the expression of caspase-3 and apoptosis protease-activating factor-1 (APAF-1) was assessed. To investigate the molecular mechanism of apoptosis induced by bLf, a major Lf-binding protein was screened using a protein microarray with bLf protein as the probe. Protein interaction was demonstrated by co-immunoprecipitation, immunofluorescence and phosphatase activity assay.
  
  
  RESULTS
  Lf directly suppressed the proliferation of the PC-14 cells by triggering their apoptosis. Lf was shown to bind specifically with a 36-kDa protein, immunoglobulin (CD79A)-binding protein 1 (IGBP1). The binding complex interacted with the catalytic subunit of protein phosphatase 2A (PP2A), thus reducing the phosphatase activity of PP2A and triggering apoptosis.
  
  
  CONCLUSIONS
  Lf binds IGBP1 and promotes the acceleration of cellular apoptosis.
authors.affiliation: Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Dongping
authors.initials: D
authors.lastname: Li
authors.forename: Shingo
authors.initials: S
authors.lastname: Sakashita
authors.forename: Yukio
authors.initials: Y
authors.lastname: Morishita
authors.forename: Junko
authors.initials: J
authors.lastname: Kano
authors.forename: Aya
authors.initials: A
authors.lastname: Shiba
authors.forename: Taiki
authors.initials: T
authors.lastname: Sato
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D018832:Molecular Chaperones; D040081:Protein Array Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490467:IGBP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D007781:Lactoferrin